On February 10, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to amezalpat (TPST-1120), an oral, small molecule, selective PPAR⍺ antagonist for the treatment of patients with hepatocellular carcinoma (HCC) (Press release, Tempest Therapeutics, FEB 10, 2025, View Source [SID1234650138]).
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"We are thrilled to receive Fast Track designation from the FDA," said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D of Tempest. "This designation, following the Orphan Drug designation granted last month, reinforces the promise of amezalpat as a potential treatment option for patients affected by HCC. We look forward to working closely with the FDA and foreign regulatory agencies to develop amezalpat with the goal of bringing this promising therapy to patients."
This is the second regulatory designation granted to amezalpat. The company announced in January that the U.S. FDA granted amezalpat with Orphan Drug Designation (ODD) following positive data across multiple key study efficacy and safety endpoints in a global randomized Phase 1b/2 clinical study evaluating amezalpat plus standard-of-care atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic HCC. Notable positive outcomes of the randomized comparison include a six-month improvement in median overall survival (OS) with a hazard ratio (HR) of 0.65 for patients receiving the amezalpat combination therapy. In addition, a survival benefit from the addition of amezalpat was preserved in key sub-populations including PD-L1 negative disease, which is consistent with amezalpat’s proposed mechanism of action to target both the tumor cells directly and the patient’s immune system.
About Hepatocellular Carcinoma
HCC is an aggressive cancer with rising mortality and is projected to become the third leading cause of cancer death by 2030.ii Every year, more than 900,000 people worldwide are diagnosed with HCC.iii Incidence and mortality are highest in East Asia and are increasing in parts of Europe and the US.iv In the US, HCC represents the fastest-rising cause of cancer-related death. iii
Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.v
Even if diagnosed in the early stage, an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery.vi Early recurrence is associated with poorer prognosis and shorter survival. v,vii Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.vi
About Amezalpat
Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggests that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a global randomized phase 1b/2 study in first-line HCC patients, amezalpat in combination with atezolizumab and bevacizumab showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to patients receiving atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.
About Fast Track Designation
Fast Track designation is intended to help rapidly advance the development and review processes for promising therapeutic candidates for serious conditions that may fill an unmet medical need. Clinical programs with Fast Track designation may benefit from early and frequent communication with the FDA throughout the regulatory review process and may also be eligible for accelerated approval and priority review when relevant criteria are met.